Reciprocal Induction and Repression of Serine Dehydratase and Phosphoglycerate Dehydrogenase by Proteins and Dietary‐Essential Amino Acids in Rat Liver

Abstract

The impact of protein nutrition upon serine biosynthesis and catabolism in rat liver was investigated by determining the activity of two key enzymes in the pathway of serine metabolism, phosphoglycerate dehydrogenase on the pathway leading from pyruvate to serine, and serine dehydratase on the catabolic way transforming serine to pyruvate. It was found that increasing the protein content of the diet induces serine dehydratase and represses reciprocally phosphoglycerate dehydrogenase. For casein, a protein of high nutritive value, the activities of both enzymes are at equilibrium at the 20% dietary protein level, which is near the optimum casein level for rat growth. With gluten, a protein of low nutritive value, equilibrium is reached at almost the same dietary protein level (22%), although optimal growth is not attained prior to the 50% dietary protein level. In this comparison, there is no correlation between the nutritive value of the proteins (growth measurement) and their regulatory action on the two enzymes tested. Extension of the studies to other proteins, such as egg, showed however that egg, the protein of highest nutritive value, has also the greatest effect on enzyme regulation. The conclusion is that a certain relationship between nutritive value and enzyme‐regulatory action exists, but that the determining factors (amino acids) are partly different. The role of individual dietary amino acids upon serine metabolism was therefore investigated. It was first shown that only the essential amino acids as a group were responsible for the reciprocal induction and repression of the two enzymes. By feeding amino acid mixtures lacking one essential amino acid at a time to the animals, we established subsequently that four essential amino acids only, i.e. methionine, tryptophan, threonine and valine are active in regulating the two enzymes. Cystine influences only phosphoglycerate dehydrogenase. The enzyme‐regulating action of proteins can thus be expressed in terms of their content in “active” amino acids, whereas their nutritive value depends on the presence of all essential amino acids. The similar behaviour of casein and gluten in enzyme regulation in spite of the great difference in nutritive value is thus fully explained, since the deficient amino acid in gluten, i.e. lysine, is not active in the regulation of the two enzymes studied. Finally a coherent theory for the reciprocal serine dehydratase repression and phosphoglycerate dehydrogenase induction in rat liver by lack of an “active” amino acid is proposed. It is based on the presence of a posttranscriptional represser which both inhibits messenger translation and promotes messenger degradation, and on the fact that the translation of small proteins is less impeded by amino acid deficiency than that of bigger polypeptide chains. Copyright © 1973, Wiley Blackwell. All rights reserved